Background

For organisms to adapt to changing environments, the acquisition of new traits through mutations is essential. However, an excessive number of mutations can threaten cell survival and compromise genome stability. For this reason, organisms have maintained mechanisms to precisely repair errors that occur during replication, thereby safely preserving genetic information. Until now, the scientific community believed that mutations occur at a relatively uniform frequency or randomly across the genome. In particular, for evolutionarily ancient eukaryotes such as marine unicellular algae, it was not clearly known how the influx of foreign genes was suppressed. Previous studies have focused primarily on mammals, including humans, and major plant models. As a result, understanding how the primary producers of the ecosystem, microalgae, maintain genetic integrity in the face of frequent viral invasions has remained a long-standing gap.

Key Findings

An international research team, including the Joint Genome Institute (JGI) of the U.S. Department of Energy and the French National Center for Scientific Research (CNRS), tracked the mutational characteristics of Bigelowiella natans, a marine phytoplankton. The researchers conducted mutation accumulation experiments by long-term culturing this microalgae in the laboratory for hundreds of generations. Subsequently, changes in the nuclear genome were observed using next-generation sequencing, revealing unexpected findings. The overall basal single-base mutation rate of the genome was maintained at a very low level of approximately 3.5 × 10^-10 per base pair per generation. However, two specific viral-origin genome regions integrated into the host genome showed a completely different pattern. The mutation rate of these virus-derived regions reached approximately 6 × 10^-7 per generation. This represents a mutation rate 1,700 times faster than in normal regions. Surprisingly, this hypermutation phenomenon does not occur randomly. It was observed to be concentrated only at specific dinucleotide (TpA dinucleotide) positions where thymine and adenine are consecutively linked in the sequence. Transitions, in which adenine and thymine are converted to cytosine and guanine, account for the majority of the mutations at this location. This indicates that there is a targeted mutation activity that is precisely regulated by the cell, rather than random errors.

Significance and Prospects

This discovery shows remarkable similarities to the molecular mechanisms that vertebrates, including humans, use to combat invading foreign viruses. Animal cells use genome editing enzymes such as APOBEC and ADAR as defense mechanisms to modify and inactivate viral genetic information. This study has revealed that a similar primitive genome editing immune mechanism is preserved and functioning in eukaryotic evolutionary lineages other than vertebrates. This suggests that the mechanism for protecting genome integrity in response to the threat of foreign genes emerged very early in the history of life. However, this study focused on a single species of microalgae in a precisely controlled laboratory environment. Whether the same phenomenon occurs widely in other diverse groups of protists in natural environments remains to be demonstrated. Furthermore, it is necessary to investigate whether hypermutation induces energy consumption or other physiological side effects in the cell itself.